The present invention relates to a method for determination of the local distribution of nuclear magnetic resonance spectrum of the nucleus of an atom to be analysed and/or inhomogeneities in the magnetic field by employing NMR nuclear spin imaging methods.
Nuclear magnetic resonance phenomenon (hereinafter NMR) has been known since the 1940s. The first experiments were carried out by Bloch and Purcell in 1946. Since then, the phenomenon has been applied in the fields of physics, chemistry and medicine.
NMR is based on the fact that the nuclei of certain elements have a magnetic moment. Among these are e.g. .sup.1 H, .sup.19 F and .sup.31 P, whose nuclear spin quantum number I=1/2. The magnetic moment .mu. of a nucleus is proportional to the spin quantum number I of the nucleus: EQU .mu.=.gamma. I, (1)
wherein
.gamma.=a gyromagnetic ratio depending on nucleus PA1 =h/2.pi.; h is Planck's constant
The behaviour of a cluster of nuclei in an external magnetic field can be analysed either by means of quantum mechanics or classical mechanics. The latter is a more perceptual approach. It can be presumed that nuclei are small bar magnets on which the rotation or spin of nuclei around their own axis generates not only a magnetic moment but also an impulse moment.
If a sample with a substantial number of e.g. .sup.31 P atoms is placed in an external magnetic field B.sub.o, the majority of magnetic moments of the nuclei of said atoms will be aligned parallel with said external magnetic field and the resultant will generate so-called net magnetization which is parallel to the external field. Said net magnetization can be deflected from the direction of the external magnetic field by exciting the sample with electromagnetic energy at a frequency which fulfils the resonance condition EQU W.sub.o =.gamma.B.sub.o =2.pi..function.o (2)
f.sub.o =so-called Larmor frequency.
The deflected magnetization precesses around the direction of the external magnetic field at a frequency which corresponds to said Larmor frequency. This precessing magnetization can be detected by placing outside the target an induction coil for inducing a signal voltage having Larmor frequency and being proportional to the precessing net magnetization.
In order to detect the precession of nuclear magnetization by means of an induction coil, the magnetization precession of the nuclei must proceed phase-coherently. This status prevails immediately after the excitation pulse but, due to the relative interactions of the nuclei of a sample, the nuclei will be exposed to magnetic fields slightly different from one another and, thus, the precession frequencies thereof differ from each other and the precession coherence will decline. The decline of coherence leads to the decay of an inducing signal and this exponential process is characterized by a relaxation time T.sub.2 (so-called spin-spin relaxation time).
The deflected magnetization returns gradually to the direction of the external magnetic field B.sub.o, i.e. the nuclear system delivers to its environment the energy received thereby during the excitation pulse. The nature of this process is also exponential and it is characterized by a relaxation time T.sub.1 (so-called spin-lattice relaxation time).
The magnetic fields created by the molecule and ambience also generate a plurality of resonance frequencies, i.e. a signal being induced has a spectrum which depends not only on polarizing magnetic field B.sub.o but also on the chemical properties of a sample, including physical state, molecular structure and other ingredients of a sample. The effect of a sample itself on the resonance spectrum is called a chemical shift, marked as .delta., which is measured as a frequency deviation relative to a known reference frequency. The reference frequency is obtained by measuring the resonance of a known material in the presently used field B.sub.o.
Said frequency deviations are millionths of a basic frequency and, thus, .delta. is often quoted in units ppm (part per million).
In NMR spectroscopy, a sample is placed in a homogeneous magnetic field and the nuclei to be analysed are excited by means of a short-time radio-frequency pulse. Immediately after the excitation, a resonance signal inducing to a signal coil is amplified, detected, converted from analog to digital and stored in the memory of a computer. The computer subjects the stored signal to Fourier transformation, resulting in the spectrum of said signal. On the basis of the intensity of the components of a thus obtained spectrum and on the basis of the deviations from reference frequencies it is possible to conclude the molecular structure of a matter or to identify ingredients contained in the sample by comparing the obtained spectrum with tabulated spectra. The described method is called pulse NMR spectroscopy and it has been disclosed e.g. in the reference Ernst et al.: Rev. Scient. Instr. Vol. 37, 93, 1966.
In 1973, Professor Lauterbur was the first to introduce an idea of applying the NMR phenomenon to imaging or to mapping the distributions of concentrations and relaxation times of an atom to be analysed (Nature Vol. 242, Mar. 16, 1973, p. 190-191).
Hereinafter a method of mapping the distributions of NMR parameters will given a general term nuclear spin imaging method.
A plurality of nuclear spin imaging methods have been developed. These have been described e.g. in the following Patent publications: Ernst: U.S. Pat. No. 4,070,611, Mansfield: U.S. No. 4,165,479; Garroway et al: U.S. No. 4,021,726; Moore et al: No. 4,015,196; Hutchinson et al: WO No. 81/02789; Sepponen: FI appln. No. 824343. A review on various imaging methods has been disclosed e.g. in the reference Bottomley: Rev. Sci. Instruments, Vol. 53, 9 pp. 1319 . . . 1337, 1982.
These methods, as well as other nuclear spin imaging methods, are characterized in that, during the signal recording, there is placed over a zone to be imaged a magnetic field gradient or a so-called read out-gradient. A magnetic field gradient results in that the signal being recorded contains positional information as frequency-encoded but recording of a chemical spectrum without special arrangements is impossible.
One way of collecting the local distribution of the spectrum of a chemical shift has been disclosed in the reference P. Bendel et al: Journal of Magnetic Resonance, Vol. 38, 343 . . . 356, 1980. The described method is based on the mathematical processing of the signals recorded during oppositely directed magnetic field gradients so as to find out the spectral information. The mapping of NMR characteristics is based on repeatedly exciting a sample by a radio-frequency pulse, followed by recording a NMR signal while a magnetic field gradient is turned on. The direction of a gradient following each excitation differs from the preceding gradient and, thus, projections of a sample are obtained from different directions. The projections obtained are used to reconstruct, e.g. as described in the reference Brooks et al. (Radiology, Vol. 117, 561, 1975), the internal structure of a target. The spectroscopic information of a chemical shift, in turn, can be mathematically reconstructed because of the fact that the frequency deviation caused by a chemical shift does not depend on the direction of an external field gradient. This method requires highly complicated data processing as well as the use of projections for building an image. On the other hand, the method cannot be readily applied to other prior art imaging methods described, in addition to the above publications, in the reference Edelstein et al: Physics in Medicine et Biology, July 1980, No. 4, pp. 751 . . . 756.
Other approaches for the determination of the local distribution of a chemical shift is to selectively excite only those atomic nuclei of a component to be analysed, which have a certain chemical shift, and thereafter to record a nuclear magnetic resonance signal being induced. However, this method suffers from several major drawbacks. First of all, in order to determine the spectrum of a chemical shift, the imaging process must be repeated a number of times. Secondly, three-dimensional targets cannot be mapped by using a so-called selective excitation since, during the excitation phase, it is not possible to use a magnetic field gradient for limiting an imaging range. Naturally, it is plausible to employ methods suitable for three-dimensional imaging, one example of those having been described e.g. in the cited Patent publication Ernst: U.S. Pat. No. 4,070,611, Sepponen: FI appln. No. 824343, or Brown: U.S. Pat. No. 4,319,190. However, this only produces an image of one spectral component and, hence, the total imaging time becomes impractically long. Furthermore, the magnetic field of such apparatus must be highly homogeneous over the entire volume to be imaged which, e.g. when dealing with a human body, is technically very difficult or even practically impossible.
Moreover, the following Patent publications Abe et al: U.S. Pat. No. 3,932,805; Abe et al: U.S. Pat. No. 4,240,439; Damadian: U.S. 3,789,832; Damadian: DE(OS) No. 2 946 847; and Sepponen: FI 58868 disclose various methods of orientating an external magnetic field to be placed over a target in a manner that the resonance condition is only fulfilled within a limited range that can be shifted electrically or mechanically inside a target being analysed. A drawback in these methods is that, if the effort is made to map the local distribution of the nuclear magnetic spectrum of an element to be analysed, the target volume must be examined point by point. Thus, the analysis takes a long time and the movements of a target, such as respiration, peristalsis of the intestines etc., lead to inaccuracies in mapping. Instruments based on this method are at the moment manufactured e.g. by Oxford Instruments (England), whose "Topical Magnetic Resonance" apparatus, fitted with a superconductive magnet, is capable of producing a .sup.31 P-spectrum within a carefully restricted volume of a target.
It is also prior known to localize a volume from which a nuclear magnetic resonance spectrum is measured by means of a suitable signal coil. Thus, the geometry of a signal coil is used to restrict the zone from which a signal is received. By using the same signal coil also as an excitation coil and by changing the duration and/or amplitude of an excitation pulse, the mapping can be effected in the direction perpendicular to the plane of said signal coil. A drawback in this method is that, if it is desired to analyse areas far away from the signal coil, the positional accuracy deteriorates rapidly as the distance grows. In view of this, the method has been used e.g. for mapping the .sup.31 P-spectrum of cerebral cortex by means of surface coils from outside the skull.
Furthermore, the reference Brown U.S. Pat. No. 4,319,190 discloses mapping of a nuclear magnetic resonance spectrum in a manner that the signal is recorded without a magnetic field gradient (read gradient). A drawback in this method is a long imaging time. For example, for producing a 64.times.64 image it is necessary to collect 64.sup.2 signals and, if the repetition interval of pulses is 1 s, the imaging time will be 68 minutes.
The reference Burl et al: GB Patent application No. 2057142 anticipates a method wherein the signal is collected in a manner that the direction of a read gradient is repeatedly reversed and generated this way is a so-called spin-echo train which is so effected by a chemical shift that a chemical spectrum can be produced by carrying out the Fourier transform in the direction of said train. A drawback in this method is the relatively great gradient field strength, which is necessary and may involve health hazards and which, by increasing the band width of a signal, reduces the signal-to-noise ratio. In addition, the finite rise times of gradients result in phase errors in a signal to be collected.
Further known on the basis of the reference Cox and Styles: Journal of Magnetic Resonance Vol. 40, p. 209, 1980 is the application of a so-called "Rotating Frame Zeugmatography" method, disclosed in the reference Hoult: Journal of Magnetic Resonance Vol. 33, p. 103, 1979, to the mapping of the local distribution of a chemical shift. Drawbacks in this method include technical difficulties in the application thereof, e.g. generation of a required radio-frequency field gradient and the required high RF output especially in the case of a human body as well as the fact that the method is difficult or impossible to apply to a more than one-dimensional case.
A further reference Aue et al: Journal of Chemical Physics, Vol. 64, No. 5, Mar. 1, 1976, p. 2229, discloses a principle of two-dimensional spectroscopy, one application of which comprises also so-called Fourier imaging methods, said principle being applied to determination of the local distribution of a chemical shift in references Hall et al: Journal of Magnetic Resonance, Vol. 50, pp. 161 . . . 164, 1982 and Maudsley et al.: Journal of Magnetic Resonance, Vol. 51 pp. 147 . . . 152, 1983, which also have no magnetic field gradient coupled over a target during signal collection and which require a rather long imaging time.
The methods described in these references are very similar to that set forth in reference Brown: U.S. Pat. No. 4,319,190.